Synthesis of pyrazoles and indazoles

Recent Literature

An iron-catalyzed route for the regioselective synthesis of 1,3- and
1,3,5-substituted pyrazoles from the reaction of diarylhydrazones and vicinal
diols allows the conversions of a broad range of substrates.
N. Panda, A. K. Jena, J. Org. Chem., 2012,
77, 9401-9406.

The reaction of terminal alkynes with n-BuLi, and then with aldehydes,
followed by the treatment with molecular iodine, and subsequently hydrazines or
hydroxylamine provided the corresponding 3,5-disubstituted pyrazoles or
isoxazoles in good yields and with high regioselectivity.
R. Harigae, K. Moriyama, H. Togo, J. Org. Chem., 2014,
79, 2049-2058.

1,3-Diketones, which were synthesized in situ from ketones and acid
chlorides, were converted into pyrazoles by the addition of hydrazine. This
method allows a fast and general synthesis of previously inaccessible
pyrazoles and synthetically demanding pyrazole-containing fused rings.
S. T. Heller, S. R. Natarajan, Org. Lett.,
2006, 8, 2675-2678.

A simple, highly efficient, 1,3-dipolar cycloaddition of diazo compounds and
alkynyl bromides gives 3,5-diaryl-4-bromo-3H-pyrazoles or the
isomerization products 3,5-diaryl-4-bromo-1H-pyrazoles in good yields.
The diazo compounds and alkynyl bromides were generated in situ from
tosylhydrazones and gem-dibromoalkenes, respectively. The reaction system
exhibited high regioselectivity and good functional group tolerance.
Q. Sha, Y. Wei, Synthesis, 2013, 45,
413-420.

A regioselective synthesis of tri- or tetrasubstituted
pyrazoles by the reaction of hydrazones with nitroolefins mediated
with strong bases such as t-BuOK exhibits a reversed, exclusive
1,3,4-regioselectivity. Subsequent quenching with strong acids such as TFA is
essential to achieve good yields. A stepwise cycloaddition reaction
mechanism is proposed.
X. Deng, N. S. Mani, Org. Lett., 2008,
10, 1307-1310.

Two general protocols for the reaction of electron-deficient N-arylhydrazones
with nitroolefins allow a regioselective synthesis of 1,3,5-tri- and
1,3,4,5-tetrasubstituted pyrazoles. Studies on the stereochemistry of the key
pyrazolidine intermediate suggest a stepwise cycloaddition mechanism.
X. Deng, N. S. Mani, J. Org. Chem., 2008,
73, 2412-2415.

Alumino-heteroles are obtained from simple precursors in a fully chemo- and
regioselective manner by a metalative cyclization. The carbon-aluminum bond is
still able to react further with several electrophiles, without the need of
transmetalation providing a straightforward access to 3,4,5-trisubstituted
isoxazoles and 1,3,4,5-tetrasubstituted pyrazoles.
O. Jackowski, T. Lecourt, L. Micouin, Org. Lett., 2011,
13, 5664-5667.

Various 1-acyl-5-hydroxy-4,5-dihydro-1H-pyrazoles have been prepared in
good yields from the corresponding 2-alkyn-1-ones. The resulting
dihydropyrazoles undergo dehydration and iodination in the presence of ICl and
Li2CO3 at room temperature to provide 1-acyl-4-iodo-1H-pyrazoles.
J. P. Waldo, S. Mehta, R. C. Larock, J. Org. Chem., 2008,
73, 6666-6670.

A series of 4-substituted 1H-pyrazole-5-carboxylates was prepared from
the cyclocondensation reaction of unsymmetrical enaminodiketones with tert-butylhydrazine
hydrochloride or carboxymethylhydrazine. The compounds were obtained
regiospecifically and in very good yields.
F. A. Rosa, P. Machado, P. S. Vargas, H. G. Bonacorso, N. Zanatta, M. A. P.
Martins, Synlett, 2008,
1673-1678.

An easy and efficient copper-catalyzed reaction for the synthesis of
polysubstituted pyrazoles from phenylhydrazones and dialkyl
ethylenedicarboxylates tolerates a range of functionalities, and the
corresponding adducts can be obtained in moderate to good yields.
C. Ma, Y. Li, P. Wen, R. Yan, Z. Ren, G. Huang, Synlett, 2011,
1321-1323.

The reaction of diazo(trimethylsilyl)methylmagnesium bromide with aldehydes or
ketones gave 2-diazo-2-(trimethylsilyl)ethanols, which were applied to the
synthesis of di- and trisubstituted pyrazoles via [3+2] cycloaddition reaction
with ethyl propiolate or dimethyl acetylenedicarboxylate.
Y. Hari, S. Tsuchida, R. Sone, T. Aoyama, Synthesis, 2007,
3371-3375.

2H-Indazoles are synthesized using a copper-catalyzed one-pot,
three-component reaction of 2-bromobenzaldehydes, primary amines, and sodium
azide. The catalyst plays the key role in the formation of C-N and N-N bonds.
This method has a broad substrate scope with a high tolerance for various
functional groups.
M. R. Kumar, A. Park, N. Park, S. Lee, Org. Lett., 2011,
13, 3542-3545.

Various N-aryl-1H-indazoles and benzimidazoles were synthesized
from common arylamino oximes in good to excellent yields depending upon the base
used in the reaction. Triethylamine promoted the formation of benzimidazoles,
whereas 2-aminopyridine promoted the formation of N-arylindazoles.
B. C. Wray, J. P. Stambuli, Org. Lett., 2010,
12, 4576-4579.

Azobenzenes were readily acylated at the 2-position with aldehydes in good
yields through a Pd-catalyzed C-H functionalization in the presence of TBHP. The
obtained acylated azobenzenes could be efficiently converted into the
corresponding indazole derivatives in nearly quantitative yields.
H. Li, P. Li, L. Wang, Org. Lett., 2013,
15, 620-623.

The 1H-indazole skeleton can be constructed by a [3 + 2] annulation
approach from arynes and hydrazones. Under different reaction conditions, both
N-tosylhydrazones and N-aryl/alkylhydrazones can be used to afford
various indazoles.
P. Li, C. Wu, J. Zhao, D. C. Rogness, F. Shi, J. Org. Chem., 2012,
77, 3127-3133.

A general two-step synthesis of substituted 3-aminoindazoles from
2-bromobenzonitriles involves a palladium-catalyzed arylation of benzophenone
hydrazone followed by an acidic deprotection/cyclization sequence. This
procedure offers a general and efficient alternative to the typical SNAr
reaction of hydrazine with o-fluorobenzonitriles.
V. Lefebvre, T. Cailly, F. Fabis, S. Rault, J. Org. Chem., 2010,
75, 2730-2732.